Abstract
Dendritic cells’ (DCs) ability to present antigens and initiate the adaptive immune response confers them a pivotal role in immunological defense against hostile infection and, at the same time, immunological tolerance towards harmless components of the microbiota. Food products can modulate the inflammatory status of intestinal DCs. Among nutritionally-derived products, we investigated the ability of quercetin to suppress inflammatory cytokines secretion, antigen presentation, and DCs migration towards the draining lymph nodes. We recently identified the Slpi expression as a crucial checkpoint required for the quercetin-induced inflammatory suppression. Here we demonstrate that Slpi-KO DCs secrete a unique panel of cytokines and chemokines following quercetin exposure. In vivo, quercetin-enriched food is able to induce Slpi expression in the ileum, while little effects are detectable in the duodenum. Furthermore, Slpi expressing cells are more frequent at the tip compared to the base of the intestinal villi, suggesting that quercetin exposure could be more efficient for DCs projecting periscopes in the intestinal lumen. These data suggest that quercetin-enriched nutritional regimes may be efficient for suppressing inflammatory syndromes affecting the ileo-colonic tract.
Highlights
Quercetin is among the best known phytochemicals able to impact different aspects of human health [1]
Dendritic cells’ (DCs) extensions into the intestinal lumen were more frequent at the tip of the villi, we investigated if the presence of quercetin in the lumen could determine a gradient of Slpi expression from the tip to the base of the villi
We recently demonstrated that quercetin-exposed DCs from wild-type (WT) mice reduce their ability to release tumor necrosis factor alpha (TNFα), interleukin 1 alpha, 1 beta, 6, 10 and 12 (IL-1α, IL-1β, IL-6, IL-10, and IL-12) following LPS administration [10,11] and that Slpi expression was a non-redundant checkpoint required for quercetin-mediated TNFα secretion suppression [32]
Summary
Quercetin is among the best known phytochemicals able to impact different aspects of human health [1]. We recently demonstrated that murine dendritic cells, previously exposed to quercetin, suppress inflammatory pathways induced by LPS administration [10,11,12]. Recently have tolerogenic DCs been characterized [17,18,19]. The inflammatory abilities of DC progenitors are dynamically regulated by the local milieu. In the intestine, incoming progenitors adapt to the temporary need of the tissue, usually becoming inflammatory-impaired DCs; traumatic events and/or hostile infections can change the intestinal milieu that may become inflammatory permissive [23]. DCs polarization in the intestine represents a paradigm for the induction of tolerogenic DCs—a dynamic imprinting mediated by the host secreted factors [24], the microbiome [25,26], and nutritionally-derived factors [27]
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